Total parenteral nutrition can be defined as the feeding of nutrients by means of infusion into the bloodstream of patients who are unable to digest food properly as a result of disease, surgery, or in the case of premature infants, premature development thereof.
For example, total parenteral nutrition has been successfully employed with patients having gastrointestinal disorders, such as ulcerative colitis, Crohn's disease, ischemic bowel infarction, short bowel syndrome, malabsorption due to radiation enteritis, intestinal fistulas, cancers of the gastrointestinal tract, severe dumping syndrome, and total gastrectomy.
Premature infants have also benefited by total parenteral nutrition, as well as infants having chronic diarrhea or congenital gastrointestinal anomalies.
Home care using infusion such as total parenteral nutrition has been successfully employed in the treatment of pediatric patients having serious conditions such as AIDS, acidemia, dumping syndrome, Batten-Mayou disease, those recovering from bone marrow transplants, Crohn's disease, Fanconi's syndrome, glycogen storage disease, cellulitis, facial rhabdomyosarcoma, Ewing's sarcoma, cerebral palsy, seizure disorder, cystic fibrosis, acute myelocytic and lympo-cytic leukemia, Stevens Johnson syndrome, systemic lupus, erythematosus, tyrosinuria, hemolytic uremic syndrome, and many other disorders.
In the above mentioned conditions, total parenteral nutrition (TPN) has been successfully employed over long term periods. It has been employed for as long as ten or more years, as well as for shorter temporary periods, during which time the initial underlying condition is given a chance to heal itself.
Patients suffering from the above bowel disorders exhibit general malnutrition with the consequent loss of weight, muscular weakness, poor wound healing, reduced immunocompetence, and general impeded recovery from primary illnesses.
As a general requirement, the body must be supplied daily with adequate amounts of carbohydrates, proteins, fats, vitamins, minerals and water. The actual makeup of the TPN liquid is individually established for each patient and is produced to conform to a doctor's prescription. A typical composition of TPN liquid includes dextrose or glucose, amino acids, and electrolytes in the form of various minerals and water. Vitamins, other minerals, fatty acids, and medicines, are generally not compounded with the above materials but are rather combined just prior to infusion with the TPN solution.
Infusion of the TPN solution within the body takes place by means of a catheter which has been implaced within a large vein close to the heart. The catheter insertion is made under a local anesthetic into the anterior upper abdominal wall and tunneled subcutaneously to the target vein, which can be a cephalic, subclavian, pectoral, thyrocervical common facial, internal jugular or external jugular vein, and thence to the superior vena cava.
The use of the central vein is necessary to prevent thrombosis or clotting, which would occur if a smaller peripheral vein in the hand or arm were used.
The other end of the catheter is tunneled under the skin and exits in the middle of the chest. It incorporates a dacron velour cuff that lies under the skin in order to allow the body tissue to grow into the cuff and anchor the catheter.
Once the catheter is implaced and covered with a cap known as a luer-lok, the patient is then ready to receive parenteral nutrition or intravenous hyperalimentation, which is used interchangeably in this specification.
The foregoing described feeding of parenteral solutions has been used in hospitals since about 1966 and has been successfully adapted in recent years for use at home.
Most commonly , the TPN solution is contained within the sterile clear plastic bag or other container such as a bottle. A tube from the TPN container is provided with a luer-lok connection.
The preferred method of infusion is to connect the tube from the container of TPN liquid to the patient's catheter by means of the luer-lok connection. Control of the flow of the solution throughout the prescribed number of hours is provided by means of an electronic infusion pump or positive pressure pump. Ideally, the infusion takes place during sleep so that the patient is not inconvenienced during the day and can resume normal activities.
It can be appreciated that since the TPN liquid is directly infused into the bloodstream that it is of paramount importance not to introduce any organisms into the body through the TPN solution.
It is to the aseptic compounding of pharmaceutical liquids, especially parenteral liquids, that this invention is directed, as well as to the process for their preparation and the apparatus which is used in conjunction therewith.
In the past, parenteral solutions were prepared separately on an individual patient prescription basis just prior to each infusion. Typically, heat sterilized dextrose solutions and heat sterilized amino acid solutions were mixed together under a laminar flow hood according to one of two methods.
According to the first method, all of the additions except the calcium gluconate and magnesium sulfate are added to and mixed with the heat sterilized amino acid solution. The calcium and magnesium components are then added to and mixed with the heat sterilized dextrose solution, followed by mixing together of the two resulting solutions.
The second individual patient prescription procedure involves mixing together the heat sterilized dextrose and heat sterilized amino acid solutions followed by the additions of the other materials and finally, the calcium and magnesium compounds.
The above procedures are known as unit mix procedures, since they are used for only one infusion of a patient. They generally are infused within one hour sometimes utilizing an inline filter of 0.22 microns.
Since unit mix solutions are made up on an individual patient basis requiring from five to fifteen manipulative steps, the opportunity for introduction of pathogenic organisms is high. However, since each unit mix solution is generally infused into a patient within about one hour from preparation, there is little danger of growth of pathogens.
By contrast, the invention and process of this application uses one connection from the mixing tank to the fill bag in which all of the solution is filtered under aseptic conditions. This minimizes the opportunity for contamination by pathogens.
The significance of the present invention is to provide uniformity of nutrition to a specific patient, since as much as a month's supply can be produced according to the process of the invention in one batch mixing. This permits the patient to rely not only on the uniformity of the TPN liquid, but also to rely on the absence of pathogens within the TPN solution. Furthermore, the process permits the manufacture of the TPN liquids at greatly reduced cost over hospital techniques by as much as sixty percent less. The reduced cost, as well as the consistency, enable many patients to be parenterally infused at home. This permits them to lead a normal life as much as possible.
The process provided by this invention specifies very specific working conditions. Non-pathogenic positive flow sterile air is caused to flow over the work surfaces and apparatus which have been treated to remove pathogenic organisms. The interior surfaces of the clean room are similarly treated. In addition, the aseptic techniques, utilizing a filtering apparatus which has also been rendered free of pathogenic organisms, coupled with a single connection from the mixing tank to the fill bag permits the cold sterilization of the TPN solutions.
By this means, novel TPN solutions can be made, if desired, from the powdered amino acids and powdered dextrose directly. Furthermore, individual amino acid profiles can be adjusted as required. In pediatric use this can be required quite often.
The TPN solutions produced hereby are capable of extended storage by as long as thirty to sixty days under refrigeration. By contrast, unit mixed solutions with their opportunities for the introduction of pathogenic organisms are probably of questionable safety after about fourteen days.